Cytohesins/ARNO: the function in colorectal cancer cells.

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) are critical regulators of cell differentiation, survival, proliferation, and migration in cancers. This study found that ARNO (cytohesin-2), an activator of the EGF and IGF-I pathways, was more highly expressed in colorectal cancer tissue than in benign adjacent colorectal tissue. When ARNO-siRNA or the chemical inhibitor SecinH3 blocked ARNO, the downstream of the EGF and IGF-I pathways decreased in colorectal cell lines HT29 and HCT116. This blocking also weakened cell proliferation, invasion, and migration in vitro. Furthermore, EGF receptor (EGFR)-dependent colorectal tumor xenografts in nude mouse exerted anti-proliferative and growth suppression effects by injecting secineH3. These data suggested that inhibiting cytohesins or ARNO as cytoplasmic activators of EGFR and IGF-I in colorectal cancer resulted in anti-proliferation, reduced invasion, decreased migration, and suppressed growth in vivo and in vitro. Therefore, cytohesins or ARNO may be a potential therapy target for some colorectal cancer

High-Resolution Detection of Periglacial Landforms Deformation Using Radarsat-2 and GF-7 Stereo Optical Imagery

In cold mountain environments, rock glaciers and talus represent common periglacial landforms. Accurate monitoring of their activity is crucial for understanding alpine kinematics. Presently, spaceborne SAR satellites monitor periglacial landform deformations mainly utilizing medium-resolution data. However, capturing surface structure deformations accurately and comprehending the movement mechanisms remain challenging. This study employs high-resolution GF-7 optical stereo images and Radarsat-2 SAR data, introducing a multibaseline persistent scatterer and distributed scatterer combined multitemporal InSAR (MT-InSAR) method to identify rock glaciers and talus landforms, as well as to analyze their deformations. Initially, rock glaciers and talus are outlined using GF-7 optical images, and digital surface models are extracted. The developed MT-InSAR method then detects the line of sight and slope-parallel deformations of these landforms. Radarsat-2 monitoring reveals that 47.5% of identified rock glaciers are classified as active, while talus deformations are less active compared to rock glaciers. By utilizing high-resolution optical and SAR satellite data, we first documented the intricate deformation features within standard rock glaciers, such as the front, lateral margins, and optionally ridge-and-furrow deformations, as well as their interaction with the surrounding terrain topography. This discovery offers evidence of gravity-driven forces impacting rock glacier movement. We have also conducted a deformation analysis of the talus, obtaining spatial deformation characteristics of typical talus. It was observed that the deformation of the talus is jointly influenced by the conditions of surface debris cover and the slope of the terrain. This study highlights the value of high-resolution optical and SAR satellites in studying periglacial geomorphology dynamics

The presence of microplastics affects <em>Sepiella maindroni</em> hatching performance and microbiota colonization

Microplastics (MPs) are a global concern regarding environmental pollution. This study evaluated the impacts of MPs with two sizes (5 µm and 0.5 µm) on hatching performance and microbiota of Sepiella japonica. The presence of MPs increased the hatching rate at some stages of the fertilization process and reduced the oxygen consumption rate at the gastrula stage. No size-dependent impact was observed. The 16S rRNA gene was sequenced to identify the flora. Clustering tags assessed species diversity in the samples with 97% similarity. Proteobacteria was the most abundant phylum in all three groups. MPs publicity appreciably modified flower structure. The most variable genera were Ralstonia, Methylophilus, and Pseudorhodoferax, which can furnish nutrients and modify the host's immune response. MPs exposure appeared to enrich beneficial bacteria in this study. The presence of MPs with a size of 5µm played a greater role in this process, which is supported by presumptive functions. However, since the adsorption of suspended MPs on aquatic eggs can have cascading effects on specific life stages of oviparous animals, regular monitoring of microbial communities is necessary after juvenile S. japonica formation to prevent disease outbreaks

SecinH3 reduced the growth of colorectal HT29 tumor xenografts.

<p>The diameter of xenograft tumor established in mice was measured by ultrasound every 2 days during treatment (diagram a). T₁ was the control group. T₂ was the SecinH3 group. The tumors of the SecinH3 group were inhibited growth obviously, after daily intraperitoneal injections of SecinH3 for more than a week. There was significant difference between the two groups in the 11^th, 14^th days after treatment. Diagram (b) and(c) represent immunohistochemical straining results for Ki-67 of tumor from mice after treated with (b) or without SecinH3(c) for 14 days, (original magnification ×200). It seams that SecinH3 decreases the expression of Ki-67 in HT29 xenografts. Diagram (d) depicts the positive expression rate of Ki-67 in the tumors of mice bearing HT29 xenografts in the 14^th day after treatment with or without SecinH3. Diagram (e) depicts the positive expression of ARNO, pEGFR in the tumors of mice bearing HT29 xenografts after treatment with or without SecinH3 for 2 weeks. The ARNO and pEGFR expression of the two groups have significant difference. The diagrams show relative phosphorylation levels after normalization for GAPDH. Data are represented as the mean ± SEM. *<i>p</i><0.05, * *<i>p</i><0.01, n = 7.</p

Cytohesins/ARNO enhanced the activation of IGF-IR.

<p>(a and b) SecinH3 and ARNO-siRNA reduced IGF-IR receptor signaling. Western blot analysis of HCT116 cells treated with SecinH3 (a) or ARNO-siRNA (b) and stimulated with IGF-1 is shown. Phosphorylation of the indicated proteins was determined by immunodetection using phosphospecific antibodies. Glyceraldehydes phosphate dehydrogenase (GAPDH) served as a loading control. The diagrams show relative phosphorylation levels after normalization for GAPDH. The untreated ligand-stimulated cells were set as 3 (<i>n</i> = 3). Data are represented as the mean ± SEM. * <i>p</i><0.05, **<i>p</i><0.01.</p

High expression levels of ARNO were correlated with increased EGFR and IGF-IR signaling in human colorectal adenocarcinomas.

<p>Patients' colorectal cancers or benign adjacent tissue consecutive sections were stained for ARNO (a), pEGFR (b), and pIGF-IR (c). Representative images of normal colorectal tissue (left column) and moderate (right column) ARNO expression are shown (original magnification ×100). The diagram in (a) shows the fraction and frequencies of tumors with background (−), weak (+), moderate (++), or strong (+++) staining for ARNO. The diagrams in (b) and (c) depict the correlation of the phosphorylation levels of respective proteins with the ARNO score (<i>p</i> = 0.012 for pEGFR, <i>p</i> = 0.031 for pIGF-IR, <i>n</i> = 36). It reveals that ARNO over expression was correlated with enhanced EGFR and IGF-IR.</p

SecinH3 reduced the proliferation and migration of HT29 and HCT116.

<p>Left column of diagram (a) are representative images of Tran swell assay of HT29 and HCT116 cells treated with SecinH3 in 0, 10, 20, and 40 µM respectively. The left pictures are the result of HT29 cells without SecinH3 (DMSO 0.2% for 48h) and with SecinH3 (20 µM for 48 h) (original magnification ×100). It seems that SecinH3 can inhibit the migration of HT29 and HCT116 cells. The results are correlation with the concentration of SecinH3 and the time. The diagrams (b) show relative cell number of HT29 and HCT116 determined by MTT assay in the presence of SecinH3 in 0, 10, 20, and 40 µM for 24, 48, and 72 h. It seems that SecinH3 can inhibit the infiltration of HT29 and HCT116 cells. The results are also correlation with the concentration of SecinH3 and the time. Data is represented as the mean ± SEM. * p<0.05, **p<0.01 (<i>n</i> = 5).</p

Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Studies investigating the association between Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and intrahepatic cholangiocarcinoma (ICC) have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship.</p> <p>Methods</p> <p>A comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated with random-effects models using Review Manager version 5.0.</p> <p>Results</p> <p>Thirteen case–control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively). For case–control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11) and 3.63 (95% CI, 1.86-7.05), respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44) and 2.60 (95% CI, 1.36-4.97), respectively.</p> <p>Conclusions</p> <p>This study suggests that both HBV and HCV infection are associated with an increased risk of ICC.</p